Study to Treat Relapsed Follicular Non-Hodgkin's Lymphoma With Radiation and Bexxar

This study has been terminated.
(PI left our institution)
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00475332
First received: May 16, 2007
Last updated: January 9, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to determine the feasibility of treating relapsed follicular lymphoma with a combination of Bexxar and External Beam Radiotherapy (EBRT). Patients will receive EBRT (20 Gy in 10 fractions) followed by Bexxar.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Follicular Lymphoma
Drug: Iodine I -01 Tositumomab (Bexxar)
Procedure: External Beam Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility Study of External Beam Radiotherapy and Iodine-131 Tositumomab (Bexxar) for Patients With Relapsed Follicular Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • The Primary Endpoint of the Study Will be to Determine the Feasibility of Combining External Beam Radiotherapy (EBRT) and Bexxar by Assessing the Toxicities Associated With the Treatment. [ Time Frame: 2 yr 3 mos ] [ Designated as safety issue: Yes ]
    13 patients will be enrolled initially and followed for 3 months. If less than 10 of these patients reach a grade III or IV toxicity, then 12 more patients will be enrolled and the study will be deemed feasible. If 11 or more of the first group experience grade III/IV toxicity, the trial will stop early.


Secondary Outcome Measures:
  • The Secondary Endpoint Will be to Assess Response Rates and Patterns of Failure in Patients Treated With Bexxar and External Beam Radiotherapy (EBRT). [ Time Frame: 2 yr 3 mos ] [ Designated as safety issue: No ]
    Tumor response to treatment is measured using the RECIST criteria: Response Evaluation Criteria in Solid Tumors which defines Complete Response, Partial Response, Progressive Disease, and Stable Disease, by using tumor measurements as seen on CT or MRI


Enrollment: 2
Study Start Date: September 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Iodine I -01 Tositumomab (Bexxar)
    Patients will be treated in two dosing phases, each phase includes two infusions. The first phase, termed "dosimetric dose," involves an intravenous administration of 450 mg unlabeled tositumomab followed by an intravenous administration of 5 mCi (0.18 GBq) of I-131 tositumomab for the purpose of determining the rate of whole body clearance of radioactivity (residence time) so that the administered activity (mCi or GBq) to deliver a 75 cGy (or 65 cGy for patients with baseline platelet count from 100,000 to 149,999/mm^3) total body radiation dose can be calculated.
    Procedure: External Beam Radiation Therapy
    All patients are to receive 20 Gy in 10 fractions of 200 cGy to the PTV
Detailed Description:

Total dose delivered and tumor size are important predictors of local control in the treatment of low-grade Non-Hodgkin's Lymphoma (NHL). The basic principle is that larger nodal masses require increased doses of External Beam Radiotherapy (EBRT) to achieve local control. Radioimmunotherapy (RIT) seems to share this same characteristic. Review of the published literature on both Bexxar and Zevalin reveals that one of the most important predictors of treatment failure is nodal volume and its apparent relationship to dose delivered by RIT. The best tumor dosimetry for RIT is from Dr. Wiseman et al reporting on the dosimetry of Zevalin (PMID:11418315). He showed that tumors ≥15 cm^3 received only 1082 cGy with Zevalin, whereas the average dose delivered in tumors <15 cm^3 was 4763 cGy. Recently, Gokhale et al (PMID:16111589) published their experience with Zevalin at Cleveland Clinic and showed a significant correlation with pretreatment tumor volume and response to therapy. In their experience, tumors ≥5 cm had an 83% rate of local recurrence versus 28% for tumors <5 cm. This dosing paradox (bigger masses, which require more dose, receive less with RIT) may be diminished by the delivery of additional EBRT. This is the hypothesis that underlies the pilot study.

The dosimetric data available for Bexxar is more heterogeneous but confirms the observations seen with Zevalin. In patients previously untreated for low-grade Non-Hodgkin's Lymphoma (NHL), Koral et al (PMID:12621015) showed an increased likelihood of achieving a complete response (CR) if tumor doses were >650 cGy. Previous work by these same authors showed a trend for larger tumor volumes receiving less dose (PMID:10994741). The most compelling data for this relationship comes from the clinical trials done using Bexxar. Both in the pivotal trial (PMID:11579112) and the recently published trial treating naïve patients (PMID:15689582), tumor volume was a significant predictor of response to Bexxar. In the pivotal trial, smaller tumor burden was the only factor predicting longer duration of response.

Whereas EBRT might be able to provide reliable radiation dose, the use of Bexxar may provide the therapeutic equivalent of central lymphatic irradiation, which would permit the use of true involved field radiotherapy. Investigators have previously noted that increased EBRT field size is associated with increased short-term and long-term toxicity. The toxicities associated with the treatment of radiotherapy are related to the site treated, but do not necessarily include the dose limiting toxicity of Bexxar, which is primarily hematologic and transient. As the toxicity of RT and Bexxar may not overlap, the combination of both may allow an increase in the therapeutic window for both radiotherapy and Bexxar therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Relapsed Stage I-IV (no evidence of bone marrow involvement) Follicular Non- Hodgkin's Lymphoma (NHF). Patients must have received at least 1 prior therapeutic regimen of chemotherapy or Rituximab and demonstrated progression as demonstrated by biopsy.
  • One or more of the relapsed sites must be 5 cm or greater in dimension as assessed on two dimensional imaging from CT or MRI scan.
  • Biopsy at time of relapse confirming continued presence of CD 20 positive follicular lymphoma.
  • No anti-cancer therapy for 3 weeks (six weeks if Rituximab, nitrosourea or Mitomycin C) prior to study initiation, and fully recovered from all toxicities associated with prior surgery, chemotherapy, or immunotherapy.
  • An IRB-approved signed informed consent.
  • Expected survival rate greater than 3 months.
  • Prestudy performance status of 0 or 1 according to the World Health Organization (WHO) criteria
  • Acceptable hematologic status within two weeks prior to patient registration, including:

    • Absolute neutrophil count (ANC) ([segmented neutrophils + bands] x total white blood cells) greater than 1,500/mm^3
    • Platelet counts greater than 100,000/mm^3
  • Female patients who are not pregnant or lactating.
  • Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician, however, abstinence is not an acceptable method).
  • Patients previously on Phase II drugs if no long-term toxicity is expected, and the patient has been off the drug for eight or more weeks with no significant post-treatment toxicities observed.

Exclusion Criteria

  • Patients with impaired bone marrow reserve, as indicated by one or more of the following:
  • Prior myeloablative therapies with bone marrow transplantation (either autologous or allogeneic) or peripheral blood stem cell (PBSC) rescue.
  • Platelet count > 100,000 cells/mm^3
  • Hypocellular bone marrow
  • Marked reduction in bone marrow precursors of one or more cell lines (granulocytic,megakaryocytic, erythroid).
  • History of failed stem cell collection
  • Presence of bone marrow involvement with follicular lymphoma (FL) > 25% based on bone marrow biopsy done within 2 months of enrollment.
  • Evidence of transformation from original FL to a more aggressive NHL histology.
  • Prior radioimmunotherapy.
  • All relapsed sites are < 5 cm in dimension as assessed on two dimensional imaging from CT or MRI scan.
  • Presence of CNS (central nervous system) involvement.
  • Presence of primary Non-Hodgkin Lymphoma (NHL) of bone.
  • Patients with HIV or AIDS-related lymphoma.
  • Patients with abnormal renal function: serum creatinine > 2.0 mg/dL.
  • Patients who have received prior external beam radiation therapy within three months of registration.
  • Patients who have received G-CSF (granulocyte colony-stimulating factor) or GM-CSF (granulocyte-macrophage colony stimulating factor) therapy within two weeks prior to treatment.
  • Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives.
  • Major surgery, other than diagnostic surgery, within four weeks.
  • Presence of anti-murine antibody (HAMA) reactivity.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00475332

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
GlaxoSmithKline
Investigators
Principal Investigator: Robert J Amdur, MD University of Florida
  More Information

Publications:

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00475332     History of Changes
Other Study ID Numbers: GSK Protocol #109407
Study First Received: May 16, 2007
Results First Received: November 28, 2011
Last Updated: January 9, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 23, 2014